Rev is a key regulatory protein of HV-1. Its function is to bind to viral transcripts and effect export from the nucleus of unspliced mRNA thereby allowing the production of structural proteins. The structure was only recently determined due to the tendency of the protein to oligomerize and aggregate. Antibody antigen binding domains (Fab and scFv) can mediate co-crystallization of refractory proteins. Protein antibody complexes were produced which generated crystals from which the structure of Rev was determined by X-ray crystallography. The high affinity anti-Rev antibody used in these structural studies is also being tested for its anti HIV-1 potential as it prevents the Rev self association required for biological activity. Anti-Rev Fab antibody when internalized into infected cells showed high anti-HIV activity. The crystal structure of the antibody bound to Rev is also being used to guide the selection of small peptide inhibitors of Rev oligomerization. Cyclic peptides (12- 18 residues in length), where the N-terminus and C-terminus are linked mimicking the loop structure in the parent antibody protein, have been shown to bind to Rev. These studies may lead small molecules targeting the HIV-1 Rev protein and hence a valuable alternative therapeutic anti-HIV treatment. Also, the functional interactions of Rev with RNA and accessory proteins are being studied with the aim of gathering structural information which may be useful for targeted anti-HIV intervention. HIV protease, a homodimeric protein is essential in the viral life cycle and a major anti-HIV drug target. We have expressed and purified a number of drug resistant forms of the protease based on multi-drug-resistant clinical HIV-1 isolates. Novel drugs which bind to these isolates are being studied by co-crystallization and the crystal structures used to rationalize and optimize drug binding.